Intracellular alkalosis induced by increasing extracellular potassium. Ionic dependence and effects of amiloride and DIDS.
The intracellular alkalinization produced when extracellular potassium concentration is increased above its normal levels was studied in the rat diaphragm muscle by determination of the steady-state distribution of [14C]-5,5-dimethyl-2,4-oxazolidinedione (DMO). Replacement of external Na+ with sucrose and Mg2+ or N-methyl-D-glucamine prevented the rise in intracellular pH. Amiloride (1 mM) also abolished the elevation of intracellular pH, while the removal of external Cl- (replaced by gluconate) or addition of 0.1 mM 4-acetamido-4'-diisothyocyanostilbene-2,2-disulfonic acid (DIDS) did not prevent intracellular alkalinization from taking place. These results suggest that in the rat diaphragm muscle a Na(+)-dependent, amiloride-sensitive transport mechanism, perhaps Na+/H+ exchange, plays a major role in the K(+)-induced intracellular alkalinization. This mechanism might account for the metabolic acidosis produced by hyperkalemia.
Altenberg
G A
GA
Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000471:Alkalosis / Q000139:chemically induced*; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
D002712:Chlorides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000584:Amiloride; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium